Bis-(trifluoromethyl)-carbanilides



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' B UOROMETHYLyCARBANILIDES Wilhelm Ernst Frick, Alter Kirchweg, Ptetiingen, Basel- Land, and Walter Stammbach, Basel, Switzerland, assignors to I. R.'Geigy A.G.,' Basel, Switzerland No Drawing. Ori application Aug. 12, 1960, Ser. No. 49,151. Divided and this application May 11, 1964, Ser. No. 374,221 Claims priority, application Switzerland, Aug. 14, 1959,

76,959/59 11 Claims. (Cl. 260--553) This application isa division of application Serial No. 49,151, filed August 12. 1960. v

- The present invention concerns new diphenyl urea derivatives having valuable insecticidal 21m properties and an atiinityto keratin fibers in agueous dispersion and which protect the treated keratin material from a ck and injury by larvae of microlepidopters (such as moths) and certain species of beetle (such as fur and carpet beetles).

Another object of the invention is a process for the production of these new diphenyl urea derivatives. A further object of the invention is the pest control agents containing these new compounds as active substances and the use of these agents for pest control, in particular for the protection of keratin material from injury by insects; the invention further concerns, as industrial product, the keratin material protected in this way from injurious insects. Inaddition, the invention also. concerns disinfectants and disinfectant cleansingagents, in particular textile washing agents and toilet soaps, which contain the new active substances as well as the use of these agents for the disinfection or simultaneous cleansing and disinfection of objects of all types, in particular also of fabrics Y containing cellulose.

It is known that halogenated diphenyl ureas have antibacterial and insecticidal properties which are particularly marked it there is a CF group in the molecule.

It has now surprisingly been found, that substituted diphenyl urea derivatives having two CF; groups in one benzene nucleus, of the general formula wherein R, represents hydrogen, a halogen atom, especially chlorine or bromine,v the trifluoromethyl radical or the nitro group,

R represents hydrogen, a halogen atom, especially chlotime or bromine, the trifiuoromethyl radical or a low molecular alkyl radical such as methyl, ethyl, propyl, isopropyl etc., preferably methyl, or a low molecular alkoxy radical, preferably the methoxy or ethoxy radical, I

R represents hydrogen, a halogen atom, especially chlorine, or the phenoxy or phenyimercapto radical which latter radicals may be substituted by one or more halogen atoms, especially chlorine, or by one or more low molecular alkyl groups such as methyl, ethyl, gapyl, isopropyl, isobutyl, n-butyl and amyl radicals,

X represents hydrogen, a halogen atom preferably chlorine, or a low molecular alkoxy radical, especially the methoxy radical,

have considerably better insecticidal activity, in particular against insects, in all stages of their development, which are injurious to keratin material such as moth larvae, fur

because of their better bactericidal activity, as disinfectant and antibacterial active ingredientsfor the production of disinfectants and also of disinfectant washing and cleansing agents. In the general Formula I, the two CF; groups are advantageously in the meta position onev with respect to the other, in particular in the 3- and 5- positions of the benzene nucleus. I

The new diphenyl urea derivatives of the general Formula I can be produced by reacting by known methods, possibly in steps, one mol of a reactive derivative of carbonic acid with one mol of each of two aminobenzene compounds of the general formulae NH; and H N position to the carbamide bridge. These compounds correspond to the formula X CF;

.1 H F: (IV) wherein X, and X, represent hydrogen, chlorine atoms or CF:

groups, and

X is hydrogen or a chlorine atom.

Preferred diphenyl urea derivatives of the above Formula IV are those which are substituted either by two chlorine atoms in the 3- and 4-positions to the car bamide bridge or by one CF, group in the 3-position; in the latter case, the 4-position of the phenyl radical can be further substituted by a chlorine atom.

Examples of suitable substituted starting aminobenzene compounds of the general Formula II are, besides aniline: 3,5 bis (triliuoromethyl) aniline, 3-trifluoromethyl-4- chloraniline, 3-trifiuoromethyl-G-chloraniline, 3-5,dichlor-, 3,4,5-trichlor-, 2,4,5-trichloro-, 2-methoxy-4,5-dichloroaniline, 3-trifiuoromethyl-i-ethoxy aniline, Z-trifluoromethyl-4,5-dichloraniline, 4-nitro 4-chloro-, 3,4-dichloro-, 2-chloro-5-trifluoromethyl aniline, S-trifluoromethyl aniline, 2,4-dichloraniline, 3-chloro-4-bromaniline, 2,4- dibromaniline, 3-chloro-4-trifluoromethyl aniline, 2,5- dichloro-4-trifluoromethyl aniline and 2-nitro-4-chloraniline; as starting materials of the general Formula II containing phenoxy or phenylmercapto groups can be mentioned: 4-phenoxy-, 3-phenoxy-, 4-(4'-chlorophenoxy)-, 2-(4'-chlorophenoxy)-5-chl0ro-, 4-(3',4-dichlorophenoxy)-, 4(2',4'-dichlorophenoXy)-, 2-(4'-chlorophenoxy)-5-trifiuoromethyl-, 2-(4'-armylphenoxy)-5-chloro-,

2 (4' chlorophenoxy) 5-methyl 2-(3',4'-dichlorophet (4'-methylphenylmercapto)-aniline.

The preferred starting aminobenzene compound of the general Formula I11 is 3,S-bis-(tritluoromethyD-anilinc. As other starting materials of the general Formula III can be mentioned: 3,5-bis-(tritluoromethyl)-4-chloraniline and 2,4-bis-(trifluoromethyl)-6-methoxy aniline.

chlorocarbonic acid phenyl esters, the acid amides or im'ides particularly urea. Principally phosgene and the chlorocarbonic acid phenyl esters are used in the stepwise reaction for the production of unsymmetrically substituted diphenyl urea derivatives of the above Formula I.

'For this purpose, these are reacted by methods known per se first with 1 mol of one of the two aminobenzene compounds of the Formula II or III. used according to the invention to form the corresponding phenyl carbamic acid chlorides or phenol esters which are then reacted with 1 mol of the other aminobenzene compound to form the diphenyl urea derivative. If desired, the reaction products of 1 mol of phosgene with 1 mol of aminobenzene compound of the Formula II or II! can be converted, also by known methods, for example by heating in inert higher boiling organic solvents such as nitrobenzene or o-dichlorobenzene while splitting otf hydrogen halide, into the phenyl isocyanates corresponding to the aminobenzene compounds listed above and then suitably chosen aminobenune compounds of the Formula III or II can be added to these compounds. symmetrically substituted derivatives of diphenyl urea according to the invention, such as e.g. 3,5,3',5'-tetra-(trifluoromethyl)-diphenyl urea, are produced advantageously by heating 2 mols of the bis-(trifluoromethyl)-aminobenzene compound with'l mol of urea or phosgene, e.g. in aqueous solution, whereupon the diphenyl .urea derivative separates direct in a pure form while ammonia or hydrochlon'c acid is split off.

.The new insecticidal derivatives of diphenyl urea are white -well crystallised substances which have defined melting points. They are practically insoluble in water but dissolve well, particularly in the warm, in organic solvents such as, e.g. dialkyl ketones, chlorobenzenes, nitrobenzene, ethylene glycol monoalkyl ethers, pyridine bases, etc.

For use in an aqueous liquor, advantageously the finely milled powders of the active substance or its solution in an organic solvent which is miscible with water, are mixed with capillary active wetting and dispersing agents such as, e.g. with the formaldehyde condensation product of naphthalene sulphonic acid or with the polyalkylene glycol ethers of phenols which contain a higher molecular aliphatic or alicyclic hydrocarbon radical as ring substituent. On stirring such preparations in aqueous. treatment liquors, milky dispersions are obtained, from which the diphenyl urea derivatives according to the invention are fixed fast to washing, milling, light and dry cleaning onto keratin fibres, in particular wool, in the warm. Keratin fibres treated in this way with a content of at least 0.1 to 0.5% of active substance are durably protected from injury by larvae of rnicrolepidopters and certain types of beetle.

Compared with the known, halogenated diphenyl ureas or those containing CF, groups, the new compounds having two CF; groups in the same benzene ring have the advantage of considerably greater activity, particularly against the injurious larvae of Attagcnus and Anthrenus species.

The following examples illustrate the production process according to the invention. Parts are given therein as parts by weight and the temperatures are in degrees centigrade.

Example I urea is 242-243 Example g or, or,

229 parts of "3,S-bis-(trifiuoromethyl)-aniline are dissolved in 800 parts of acetone. Phosgene is introduced into this solution at 35-40 and at the same time. a solution of 190 parts of sodium acetate in 500 parts of water is added dropwise. Phosgene is introduced until the solution'just becomes weakly acid. The reaction mixture is then diluted with water and the precipitate which forms is filtered otf under suction. After washing with water. it is recrystallised from methanol. The melting point of the pure 3,5,3',5'-tetra-(trifluoromethyl)-N,N'-diphenyl Example 3 (IJFI cr-Gmrr-c o-NH-Qctrr t1 00H.

Example 4 or-OoQ-cm or.

A solution of 252 parts of 3,5-bis-(tn'fluoromethyl)- phenyl isocyanate in 2000 parts of chlorobenzene is added dropwise to a previously prepared solution of 278 parts of 2-amino-4-methyl-3',4'-dichlorodiphenyl ether in 1000 parts of benzene. The mixture is heated for 6 hours at -85". After cooling, the crude product is filtered otf under suction and, after drying in vacuo, it melts at about The compound is purifiedby recrystallising twice from chlorobenzene and then melts at -192.

The following compounds can be produced as described in the .previous examples 'from carbonic acid derivatives, and corresponding starting materials of Formula II or their isocyanates, and 3,5 bis (trifluoromethyD-aniline; wool treated with these compounds is protected from injury by the larvae of moths, fur and carpet beetles.

Dlphenyl urea derivative M.P

' p or.

(CHO:C- 0-C NH.C0NH 190-191 .mc-O-o-G-cm or. 18 0-18 2 laconic (in; NH-C 0-NH w (BF:

Cl-O-SONH-CO-NH lea-188 e or. HfiOs-O-NH-tZO-NHG 182-183" On choosing 3,5-bis-(trifluoromethyl)-4-chloraniiine as starting material of the Formula 111, the following com- The diphenyl' urea derivatives of Formula I produced by the process described have considerable aflinity to keratin material and are excellently suitable, therefore, for the protection of keratin material from injury by insects, particularly for the fast-to-washing mothproofing of such types of materials, both in the raw and processed state, e.g. of raw or processed wool as well as other animal hairs, fells and furs. In addition, these compounds can be employed for the impregnation of wool and woolen articles whereby excellent mothproofing is also attained.

Apart from their insecticidal activity against the larvae of the clothes moth, the compounds of .Formula I also have such an action against the larvae of the fur and carpet beetles so that keratin materials such as blankets, woollen carpets, woollen underwear, woollen clothes v and knitted goods treated with thecompounds according to invention are protected against all types of injurious insects.

An example is given below of the application of the new active ingredients.

Example 5 0.2 part of the compound according to Example 1 is dissolved in 5 parts of glycol monomethyl ether. 5 parts of sulphonated castor oil are added to this solution which is then diluted to 6000 parts by volume with water.

Formula I according to the invention have also a very good bactericidal action.

For most purposes for which antibacterial active substances are used for disinfection, whether for the purpose of simultaneous cleaning or only for disinfection itself, it is important that the active substances retain their activity in the presence of capillary active substances. This is the case with the compounds used according to the invention as active substances so that they are excellently suitable for incorporation into disinfectant washing and eelansing agents as well. as into disinfectants which in their composition also contain'capillary active substances and which do not serve the purpose of cleansing, for example, emulsifying and dispersing agents.

For the production of disinfectant washing and cleans- 11 ing agents, the active substances of general Formula I used according to the invention are incorporated in a finely distributed form or possibly dissolved inorganic solvents into the cleansing agent which have possibly been kept in a liquid condition. In particular, capillary active' substances of an anion active type such as alkali metal soaps or ammonium soaps of higher fatty acids, salts of alkyl sulphuric acids or of aliphatic or aromatic sulphonic acids; cation active substances such as quaternary am-' monium compounds having at least one long chain aliplastic or araliphatic radical, as well as non-ionogenic substances such as the condensation products of ethylene oxide with higher alkanols, with alkyl phenols or with partial fatty acid esters of polyhydroxy compounds such as, e.g. sorbitan, are used as washing and cleansing agents.

Agents which are only intended for disinfectant purposes can be solutions, suspensions or emulsions which, apart fromthe active substances used according to the invention, possibly also contain capillary active substances, for example of the type given above. Preparations of semi-solid, ointment-like consistency can also be used as disinfectants. Disinfectants according to the invention can be applied by painting or spraying the objects to be disinfected with t preparation concerned. It is also sometimes possible to dip the objects into the preparation.

Contents of a few percent of active substances used according to the invention in the disinfectant, washing or cleansing agents, and of fractions of percentages in the disinfectant application liquors possibly used for simultaneous cleansing, are sufficient to attain effective disinfection.

It was not to have been expected that the active substances used according to the invention would retain their antibacterial activity in the presence of capillary active substances, in particular in the presence of the alkali metal soaps ofhigherjatty cigs which are the most important com" nents o washing agents. .The active substances used also have good fastness to light so that they cause practically no yellowing in soaps.

Apart from the active substance, the soaps or other washing and cleansing agents can contain the usual fillers such as alkali sulphates, carbonates or phosphates as well as the other additives usual in cleansing agents.

The disinfectant cleansing agents according to the present invention can be put to the most various uses. For example, they can be used in human and veterinary hygiene for cleansing and simultaneous protection against bacteria causing diseases either direct on the skin or via the mouth or causing perspiration odours. Examples of such infective bacteria are Staphylococcus aureus, Escherichia coli, Sarcina lutea and Scarcina alba, and of those decomposing perspiration are Proteus vulgaris, Bacillus mesenthericus and Bacillus subtilis. In such cases, the most usual cleansing agent components are soaps, but also, according to the present invention, the antibacterial active ingredients defined above can also be combined with cosmetics such as ointments, creams or skin lotions which contain other capillary active substances, for example in the form of dispersing agents.

Naturally, disinfectants can also be produced which, in addition to the active substances according to the present invention, contain other active ingredients which are suitable for increasing or modifying the action.

Disinfectant cleansing agents according to the present invention can also be used, for example, for the cleansing of textiles or leather; the ready-for-use soaking, washing, cleansing and rinsing liquors to which the antibacterial active ingredients have been added later, i.e. after dis solving the capillary active substances in water, also being washing and cleansing agents according to the present invention. Like the use thereof, they also fall within the scope of the present invention. Also, the substituted diphenyl ureas of the general Formula I can be combined with dry cleaning agent, i.e. dissolved in aliphatic or aromatic, possibly chlorinated, hydrocarbons, most of which generally also contained capillary active wetting and cleansing agents which are soluble in oil.

Finally, the antibacterial cleansing agents according to the present invention can be used also for the disinfec- Example 6 75 parts of coconut oil (saponification number 262) and 25 parts-of castor oil (saponification number 175) are saponitied at 1=15 with 120 parts of an about 15% sodium hydroxide solution. 3 parts of 3,5-bis-(trilluoromethyl)-3',4'-dichloro-N,N'-dipheny.l urea or 3,5-bis-(t'rifluoromethyl)-3',5'-dichloro N,N' diphenyl urea are then added to the still liquid soap and the mixture is homogenised well. After salting out, the soap is poured into moulds and allowed to cool. Pieces of household soap are obtained which, on being used for washing, are

characterised by a good antibacterial action.

Example 7 To produce an antibacterial toilet soap, 98 parts of soda soap filings are well mixed with 2 parts of 3,5-bis- (trifiuoromethyl)-4' chloro-N,N' diphenyl urea. The

mixture is then milled and pressed into the usual moulds.

, Example 8 A A combination of 2 parts of 3,5-bis-(trifluororrrethyl)- a 40 decyl 4'-chloro-N,N'-diphenyl urea with 25 parts of triethanolsat of n-dodecycl sulphuric acid, 1 part of n-doalcohol, 3 parts of triethanolamine sulphate, 1 part of lauric acid monoglyceride and 68 parts of water can be used as a liquid toilet soap and also as shampoo. It has a good antibacterial action.

Example 9 5 parts of 3,5,3'-tri-(tritluoromethyl)-4-chloro-N,N'- diphenyl urea, 7 parts of a non-ionogenic washing agent (obtained by condensing 2,4diamyl phenol with 10-12 mols of ethylene oxide), 30 parts of sodium metasilicate and 58 parts of tetrasodium pyrophosphate are well mixed together whereupon a cleansing agent having antibacterial properties is obtained. A 1% aqueous solution of this agent is excellently suitable as a disinfectant washing liquor for the cleansing of linen, clothes, crockery andother objects.

Example 10 A dis inhactant dry cleaning agent is obtained by dissolving 0.5 part of 3,5,3,5'-tetra-(trifiuoromethyl)-N,N'-

diphenyl urea and 5 parts of a condensation product of nonyl phenol with 15 mols of ethylene oxide in 94.5

parts of tetrachloroethane or thesarne amount of trichloroethylene. 4

Example I] An antibacterial skin cream is obtained by thoroughly mixing the following components:

13 parts of glycol monostearate, 1 part of sodium dodecyl sulphate, 2 parts of polyethylene glycol 1500, 3 parts of wax, 3 parts of viscous paratfin oil, 2 parts of wool fat, 3 parts of polyoxyethylene sorbitan mono-oleate, 6 parts of glycerine, 0:1 part of perfume, 0.1 part of phydroxybenzoic acid methylester, 2 parts of 3,S-bis-(trifluoromethyl)-3',4'-dichloro N,N' diphenyl urea. Instead of 3,5-bis-(trifluoromethyl)-3',4-dichloro-N,N'- di- Y 13 phenyl urea, also 3,5-bis-(trifluoromethyl)-4'-ch1orodiphenyl urea can -beused.

What we claim is: 1. A compound of the formula B1 F; R: C F;

NH-C O-NH- I l v X wherein the two CF radicals in nucleus I being in meta-position to each other.

2. A compound of the formula p out t I Ft 3. A compound of the formula G1 I C F;

14 4. A compound of the formula (31 CF; C]

v C V S 5. A compound of the formula I C F 0%; I i F1 6. A compound of the formula 7. The compound 3,5 bis- (trifluoromethyl)-3',4' dichloro-N,N'-diphenyl urea. v

8. The compound 3,5,3,5'-tetra-(trifluoromethyl)- N,N-diphenyl urea.

9. The compound 3,5,3'-tri-(trifluoromethyl)-4'-chloro-N,N-diphenyl urea.

- 10. The compound 3,5-bis-(tfifluoron1ethyl)-4-ch1oro- N,N'-diphenyl urea.

11. The compound 3,5-bis-(trifluoromethyl)-3',5-dichloro-N,N-diphenyl urea. Y

No references cited.

IRVING MARCUS, Primary Examiner. 

1. A COMPOUND OF THE FORMULA 